Diisopropylethylamine → 6-[4-[1-(4-Fluorophenyl)-1-methylethyl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 1675008Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1675008
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:14])([F:13])[F:12])=[N:9][N:10]=2)[N:7]=1.CCN(C(C)C)C(C)C.[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)([CH3:33])[CH3:32])=[CH:27][CH:26]=1>CN(C=O)C>[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([N:34]2[CH2:35][CH2:36][N:37]([C:2]3[CH:3]=[CH:4][C:5]4[N:6]([C:8]([C:11]([F:14])([F:13])[F:12])=[N:9][N:10]=4)[N:7]=3)[CH2:38][CH2:39]2)([CH3:33])[CH3:32])=[CH:27][CH:26]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 6136576-Chloro-3-(trifluoromethyl)-(1,2,4)triazolo(4,3-b)pyridazineHCID 673400631-[2-(4-Fluorophenyl)propan-2-yl]piperazine

Produkt 1

HCID 591497946-[4-[1-(4-Fluorophenyl)-1-methylethyl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazineAusbeute 70,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

6-Chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (120 mg, 0.54 mmol), DIPEA (0.094 mL, 0.54 mmol) and 1-[2-(4-fluorophenyl)propan-2-yl]piperazine (obtained as described in J. Med. Chem. 2007, 50, 3528) (120 mg, 0.54 mmol) in DMF (1.5 mL) were stirred and heated at 80° C. for 1 hour. The resulting solution was cooled to room temperature then applied to an SCX column and eluted with MeOH followed by 2M ammonia in methanol. Fractions containing product were combined and evaporated, then purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-[4-[1-(4-fluorophenyl)-1-methylethyl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (155 mg, 70%) as a colourless solid.

Aufarbeitung

  1. temperatureThe resulting solution was cooled to room temperature
  2. washeluted with MeOH
  3. additionFractions containing product
  4. customevaporated
  5. custompurified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length)
  6. additionFractions containing the desired compound
  7. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-52e9d7466c1647cfb2b0116223aac05b
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003649B2

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